Evaluate The Toxicity And Feasibility Of Intra-Tumoral Injection

• Sponsor: University of Massachusetts, Worcester (Other)
• Overall Status: Completed
• CT.gov ID: NCT00668382
• Collaborator: (none)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 48
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase I pilot study to evaluate the toxicity and feasibility of intratumoral injection (Glycosphingolipids) GSL alpha-GAL (beta-galactosidase) in patients with advanced, refractory solid tumors who have failed standard therapies or are not eligible for standard treatment.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Metastases	Biological: Alpha-Gal Glycosphingolipid	Phase 1

Detailed Description

Intratumoral injection of alpha gal glycolipid in experimental knockout mouse model systems incorporates into tumor cell membranes and presents these xeno-transplantation epitopes to antigen presenting cells with that particular tumor's tumor associated antigens (TAA). Thus this maneuver converts any individual tumor into an in situ tumor vaccine without the need to isolate, purify or supply TAA exogenously. The effects in these model systems demonstrate both the upregulation of cytotoxic T cells which react against the particular tumor's TAA, as well as resolution of injected primary tumor and eradication and prevention of metastatic disease at distant sites. This current study was undertaken to investigate the safety and feasibility of such an approach in humans. The major toxicity concerns are acute allergic or complement activation reactions or development of autoimmunity. The primary treatment is a single intratumoral injection of alpha gal glycolipid. The study design is a standard dose escalation design and the primary endpoint is Dose limiting toxicity at one month after injection (grade 3 or 4. Subjects are followed until death utilizing standard clinical imaging and evaluation to judge overall tumor response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: Phase I Study To Evaluate The Toxicity And Feasibility Of Intra-Tumoral Injection Of Alpha-Gal Glycosphingolipids In Patients With Advanced Or Refractory Solid Tumors
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alpha-Gal Glycosphingolipid injection Intervention: Intratumoral injection of a single dose of Alpha-Gal Glycosphingolipid (0.1 mg,1mg, 10mg)	Biological: Alpha-Gal Glycosphingolipid; Intra-tumoral injection of Alpha-Gal Glycosphingolipid to evaluate toxicity

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Greater Than Grade 3 or 4 Toxicity [1 month]

   Grade 3/4 Toxicity occurring in a participant within a month of intratumoral injection

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with solid tumors who have failed standard therapies, or are not candidates for standard therapies.

2. Patients must have at least one measurable lesion that is accessible and suitable for injection of the GSL alpha-GAL.

3. Patients should not be undergoing any active treatment with chemotherapy, radiotherapy, or steroids (either because the patient or the treating physician have decided not to employ these therapies at this time, or because they had already been tried and failed). If they have been treated with these modalities, the treatments should have been completed at least two weeks prior to date of injection of GSL alpha-GAL.

4. Patients should be judged by the investigator to be able to undergo safely the procedure needed to inject the tumor with GSL alpha-GAL.

5. Age equal or over 18 years old.

6. ECOG (Eastern Cooperative Oncology Group ) performance of less than 2. (International Normalized Ratio) INR less than 1.5 and a (Partial Thromboplastin Time) PTT no greater than normal limits within 1 week prior to intra-tumoral injection (For patients who requires invasive procedure for intra-tumoral injection).

7. Laboratory Criteria (completed equal or less 2 weeks before enrollment) Hematologic: (White Blood Cell Count) WBC equal or above 3500/millimeter-cubed or (Absolute Neutrophil Count) ANC equal or above 1500/millimeter-cubed and platelet count equal or above 100,000/ millimeter-cubed.

Hepatic: Total bilirubin equal or less 4.0 milligrams/deciliter. Renal: Creatinine equal or less 2.2 milligrams/deciliter.

1. Patients must be negative for HIV (circulating antibody), Hepatitis B (circulating antigen), and Hepatitis C (circulating antibody).

2. Patients should have an expected survival of more than 6 weeks and should not have other systemic anti-tumor treatments planned during this time frame.

Exclusion Criteria:

1. Patients who are pregnant (as determined by a positive serum HCG (Human Chorionic Gonadotropin) in patients of childbearing potential) or nursing.

2. Patients under the age of 18.

3. Patients with severe infections or septicemia.

4. Patients with a history of autoimmune disease.

5. Patients in, or about to be in, active treatment with chemotherapy or steroids.

6. Patients who refuse HIV/hepatitis testing and patients who do not sign an approved consent form.

7. Patient has received other investigational drugs within 14 days before enrollment or is expected to participate in an experimental drug study during this study treatment.

8. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655-0108

Sponsors and Collaborators

• University of Massachusetts, Worcester

Investigators

• Principal Investigator: Giles Whalen, MD, University of Massachusetts, Worcester

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Giles Whalen, Study Principle Investigator, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT00668382
• Other Study ID Numbers: UM200702
• First Posted: Apr 29, 2008
• Last Update Posted: May 15, 2013
• Last Verified: May 1, 2013

• Keywords provided by Giles Whalen, Study Principle Investigator, University of Massachusetts, Worcester: Cancerous solid tumors; Alpha-Gal Glycosphingolipids
• Additional relevant MeSH terms: Neoplasm Metastasis

Study Results

Participant Flow

Recruitment Details	Patients recruited from medical and surgical oncology clinics with currently untreatable tumors from march 2007 through June 2011
Pre-assignment Detail	No assignment to separate arms, Patients had to be off any active treatment for their advanced tumors for at least 2 weeks before entry onto study and a month after. Two subjects withdrew after screening and consent because of stroke (1) and insurance refusal(1). Two patients dropped out in the first month due to treatment needs.

Arm/Group Title	Alpha-Gal Glycosphingolipid Injection
Arm/Group Description	Intervention: Intratumoral injection of a single dose of Alpha-Gal Glycosphingolipid (0.1 mg,1mg, 10mg)
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Alpha-Gal Glycosphingolipid Injection
Arm/Group Description	Intervention: Intratumoral injection of a single dose of Alpha-Gal Glycosphingolipid (0.1 mg,1mg, 10mg)
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 63.6%
>=65 years	4 36.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (12.5)
Sex: Female, Male (Count of Participants)
Female	3 27.3%
Male	8 72.7%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Greater Than Grade 3 or 4 Toxicity
Description	Grade 3/4 Toxicity occurring in a participant within a month of intratumoral injection
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Dose escalating Phase 1 scheme: three participants for each dose cohort. The second patient in the last (10 mg) dose cohort developed and adverse event (infection at injection site) and so three more participants were entered and analyzed at that dose

Arm/Group Title	Intratumoral Injection
Arm/Group Description	Single Intratumoral injection of Alpha Gal Glycosphingolipid. Three dose cohorts (0.1mg, 1mg, 10mg)
Measure Participants	11
Number [participants]	1 9.1%

Adverse Events

Time Frame	Over one month
Adverse Event Reporting Description	patients followed for as long as they lived per clinical care protocols
Arm/Group Title	Intratumoral Injection
Arm/Group Description	Single Intratumoral injection of Alpha Gal Glycosphingolipid. Three dose cohorts (0.1mg, 1mg, 10mg)
All Cause Mortality
	Intratumoral Injection
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intratumoral Injection
	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)
Surgical and medical procedures
surgical site infection	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Intratumoral Injection
	Affected / at Risk (%)	# Events
Total	0/11 (0%)

Limitations/Caveats

No allergic/immune toxicity. The single toxicity/AE was bacterial infection with UGI flora at injection site following EUS (endoscopic ultra-sound) guided injection of pancreatic cancer. Added injections covered with antibiotic prophylaxis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.